A major problem in genetics has been the role of protein polymorphisms in health. The purpose of this project is to investigate the effects of different protein phenotypes on fertility and prenatal mortality, using man and horse as contrasting species. The following protein systems have been selected for specific study: transferrin, hemoglobin, histocompatibility antigens, haptoglobin, vitamin D binding protein, plasminogen, albumin, and immunoglobulins. Some of these systems are of interest because preliminary studies have indicated fertility differences associated with different genotype or mating types, or because of associations with clinical corrlates of infertility. For other systems, the demonstration of segregation distortion in one or more species has provided indirect evidence of a fertility effect. Yet other systems are of interest because, as a part of different linkage groups in the two species, they help define chromosomal regions with a known or suspected effect on fertility. Eguine and/or human data for relevant protein systems will be integrated with fertility histories and clinical data to test hypotheses regarding (a) variation in the rate of conception or spontaneous abortion according to parental genotype or mating type; (b) association of specific protein genotype with clinical correlates of infertility; and (c) patterns of segregation distortion according to mating type and fertility history. New methods will be developed for studying the components of fertility in extended pedigrees. The different types of clinical and family data available for man and horse provide an opportunity to address questions that could not be answered with more limited data on a single species. The study of segregation of homologous proteins, and homologous chromosomal regions, in two species with differing reproductive physiology, population structure, and mating patterns, will provide insight into mechanisms of selection through differential reproduction.